Actinide elements concentrate in liver, on bone surfaces, and in lung, if inhaled, and are largely retained at those sites as potentially carcinogenic radiation sources. Promotion of removal of actinides from deposition sites and excretion from the body is the only known way to reduce the radiation risk. The structure of enterobactin (EB), an efficient Fe(III)-chelating agent elaborated by enteric bacteria, and the chemical and biological similarities of Fe(III) and Pu(IV) suggested that tetrameric ligands containing the EB functional group (catechoyl, 2,3 -dihydroxybenzoic acid) would form stable Pu(IV) chelates at pH 7, but would not react with essential divalent metals. We are applying that hypothesis to develop efficient agents for actinide removal therapy. Tests of acute toxicity and Pu(IV) excretion in mice guided the design of tetrameric catechoyl amide ligands in a stepwise manner, from 3,3,3,3,-CYCAM (a cyclic, uncharged EB analogue, which formed a Pu(IV) complex that could not be excreted) to 3,4,3,-LICAMC (a straight-chain, anionic ligand with a charge cavity suitable for Pu(IV). The functional group of the CAMC ligands is terephthalic acid, 2,3 -dihydroxy-4-carboxy-benzoic acid. Preliminary studies indicate that 3,4,3-LICAMC, a) is not toxic at the 30 Mumole/kg daily dosage, b) promotes excretion of 100% circulating Pu(IV), c) accelerates biliary elimination of Pu(IV) deposited in liver, and d) removes 60% of Pu(IV) newly deposited in the skeleton. Poly-LICAMC (consisting of 14 CAMC units, mol. wt. 3,000) promoted excretion of 50% of Pu(IV) in 24 hours; and the distribution of the residual Pu(IV) suggests it will be long acting. Metabolic balance and tracer methods will be used to evaluate 3,4,3-LICAMC and poly-LICAMC further. Studies are in progress or planned to determine: a) the ability of chronic ligand administration to promote excretion of deposited Pu(IV); b) the plasma clearance rates of the LICAMC ligands to define their intervals of action; and c) the ability of poly-LICAMC, expected to be a broad-spectrum agent, to promote excretion of Am(III). Longer-range plans include synthesis and testing of LICAMC ligand with a charge cavity suitable for the larger Am(III) ion, and development of protocols and an animal model in which to test the effectiveness of orally administered 3,4,3-LICAMC.